New enantiopure 7-azanorbornane β-substituted prolines by SN2 displacements at the Cγ of the side chain

Gil, Ana M.; Orús, Ester; López‐Carrillo, Verónica; Buñuel, Elena; Cativiela, Carlos

doi:10.1016/j.tetasy.2005.08.003

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…It is interesting to note that N -acyl-7-azabicyclo[2.2.1]heptanes (Figure ) can be classified as pyramidalized amides (average χ N of 52.0°; average τ of 16.6°). The origin of nitrogen pyramidalization in N -acyl-7-azabicyclo[2.2.1]heptanes has been proposed to be due to small C–N–C angle and allylic strain between the amide substituents and the bridgehead hydrogen atoms. − In agreement with this hypothesis, increased substitution of 7-azabicyclo[2.2.1]heptane results in an increase in nitrogen pyramidalization (e.g., 5.20 , χ N of 64.5°) . Rotational barriers of 7-azabicyclo[2.2.1]heptane amides have been measured and are comparable to N -acyl-azetidines ( 5.12 , 15.0 kcal/mol; N -4-toluoyl-azetidine, 15.7 kcal/mol) .…”

Section: Acyclic Amides: N-pyramidalization 40–60°mentioning

confidence: 87%

“…302−314 In agreement with this hypothesis, increased substitution of 7-azabicyclo[2.2.1]heptane results in an increase in nitrogen pyramidalization (e.g., 5.20, χ N of 64.5°). 547 Rotational barriers of 7-azabicyclo[2.2.1]heptane amides have been measured and are comparable to N-acylazetidines (5.12, 15.0 kcal/mol; N-4-toluoyl-azetidine, 15.7 kcal/mol). 302 The intrinsic nitrogen pyramidalization in N-acyl 7-azabicyclo[2.2.1]heptanes provides an attractive scaffold for controlling cis/trans amide rotation.…”

Section: N-heterocycle Activated N-pyramidalized Amidesmentioning

confidence: 97%

“…Structurally characterized N-pyramidalized N-heterocycle-activated amides with χ N values >40° are summarized in Figure . ,,,,− In general, these amides can be divided into the following classes of amides: (1) conformationally constricted N -acyl-7-azabicyclo[2.2.1]heptanes ( 5.4 , 5.5 , 5.7 , 5.9 – 5.20 ) ,, and related derivatives, such as N -acyl-8-azabicyclo[3.2.1]octanes ( 5.2 ) and N -acyl-2-azabicyclo[2.1.1]hexanes ( 5.8 ), (2) N -acyl-pyrrolidines ( 5.1 , 5.3 ), , and (3) N -acyl-oxazolidin-5-ones ( 5.6 , 5.21 ). , N -Acyl-azetidines and N -acyl-azridines are not included because the ring strain of the small ring significantly contributes to the properties of these amides. , …”

Section: Acyclic Amides: N-pyramidalization 40–60°mentioning

confidence: 99%

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In this contribution, we provide a comprehensive overview of acyclic twisted amides, covering the literature since 1993 (the year of the first recognized report on acyclic twisted amides) through June 2020. The review focuses on classes of acyclic twisted amides and their key structural properties, such as amide bond twist and nitrogen pyramidalization, which are primarily responsible for disrupting n N to π* CO conjugation. Through discussing acyclic twisted amides in comparison with the classic bridged lactams and conformationally restricted cyclic fused amides, the reader is provided with an overview of amidic distortion that results in novel conformational features of acyclic amides that can be exploited in various fields of chemistry ranging from organic synthesis and polymers to biochemistry and structural chemistry and the current position of acyclic twisted amides in modern chemistry.

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Section: Acyclic Amides: N-pyramidalization 40–60°mentioning

confidence: 87%

Section: N-heterocycle Activated N-pyramidalized Amidesmentioning

confidence: 97%

Section: Acyclic Amides: N-pyramidalization 40–60°mentioning

confidence: 99%

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Cyclic α‐Amino Acids as Proline Mimetics

Trabocchi

Guarna

2014

Peptidomimetics in Organic and Medicinal Chemistry

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Structural diversity of bicyclic amino acids

2007

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Over the years biomedical research has been constantly oriented towards the development of new therapeutics based on bioactive peptides and their analogues. In particular, the generation of compounds having structures and functions similar to bioactive peptides, named "peptidomimetics", raised much interest among organic and medicinal chemists due to the possibility by using such compounds to improve both potency and stability of peptidic lead compounds. In the context of this research area, unnatural amino acids are of great interest in drug discovery, and their use as new building blocks for the development of peptidomimetics with high diversity level and possessing high-ordered structures is of special interest. In particular, medicinal chemistry has taken advantage of the use of amino acid homologues and of cyclic and polycyclic templates to introduce elements of diversity for the generation of new molecules as drug candidates. Bicyclic amino acids have been developed as reverse turn mimetics and dipeptide isosteres, and the constraint imposed by their structures has been reported as a tool for controlling the conformational preferences of modified peptides. Moreover, synthetic efforts have been driven to the generation of diverse structures based on the modulation of ring size and scaffold decoration by suitable functional groups. Herein is reported an overview of different classes of bicyclic amino acids, taking into account the strategies to achieve structurally diverse templates, and some implications in medicinal chemistry are also disclosed.

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New enantiopure 7-azanorbornane β-substituted prolines by SN2 displacements at the Cγ of the side chain

Cited by 8 publications

References 27 publications

Acyclic Twisted Amides

Acyclic Twisted Amides

Cyclic α‐Amino Acids as Proline Mimetics

Structural diversity of bicyclic amino acids

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